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CH264/1 Organic Chemistry II
Mechanism and Stereochemistry
Dr Andrew Marsh [email protected]
Dr David J Fox [email protected]
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Today’s Lecture
1. Cahn-Ingold-Prelog rules for stereochemical assignment
2. Enantiomers - molecules with one stereogenic centre
3. Diastereomers - molecules with two or more stereogenic centres
4. Chiral molecules without a stereogenic centre
CGW = Organic Chemistry J Clayden, N Greeves, S Warren 2nd Edition OUP 2012
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Molecular shape and asymmetry
pp. 302 – 311 CGW 2/e
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Optical Activity
pp. 309 CGW 2/e
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Assignment of stereochemistry• If an atom has four different groups around it, the centre is
STEREOGENIC and the molecule will be CHIRAL• Cahn-Ingold-Prelog sequence rules (C-I-P) are used to
assign stereochemistry to that centre• Revision: CGW p.308
If we assign a PRIORITY to these groups such that a>b>c>d and then re-draw the molecule such that the lowest priority (d) points away from us:
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C-I-P Assigning Priority
• We assign priority to the groups around the central atom according to atomic number
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Assigning Priority 2• Functional groups containing the same atom, look to the next
substituent to decide priority. e.g. butan-2-ol
• Use ‘single bond equivalents’ to decide which group takes priority. For example, a carbonyl group = 2 C-O bonds, an alkene = 2 C-C.
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Diastereomers• Chiral molecules with two stereogenic centres are called
diastereomers. Diastereomers have different physical properties such as m.p., b.p. solubility etc. Hence they are separable by standard purification techniques, unlike enantiomers.
• Certain pairs of diastereomers can be mirror images of each other and are thus enantiomers.
• Consider the reaction of butan-2-ol with 2 chloropropanoic acid.....
CGW p. 311-315
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CGW p. 315
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meso-CompoundsIf a molecule has any symmetry element e.g. internal plane of symmetry, or centre of inversion, i, it is rendered optically inactive and is designated meso-.
centre of inversion
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Examples
Mark stereogenic centres with *
Classify R or S
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Molecules without a stereogenic carbon atom
Many atoms are stereochemically well-defined and thus can be considered as stereogenic. Examples include sulfur and phosphorous.
DiPAMP - an enantiopure hydrogenation catalyst R-methylphenyl sulfoxide
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Chiral molecules without a stereogenic centre
ALLENES - axial chirality since the double bonds are hybridised at 90°
Biphenyls exhibit ATROPISOMERISMIf C-C rotation is restricted
CGW p. 319
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Helical ChiralityExamples of helical molecules include hexahelicene which can be resolved into two enantiomers. When viewed from above, the right handed helix is described as P (plus) and the left handed helix is called M (minus).
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Enantio/ diasterotopicity
A PROCHIRAL centre is one that can become stereogenic if one group is replaced by a new, different one:
Ha and Hb are HETEROTOPIC and can be assigned C-I-P prochirality descriptors
CGW p. 820-823
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Classification of prochiral centres
We simply use an extension of the Cahn-Ingold-Prelog rules for stereochemical nomenclature to designate the heterotopic atoms pro-R or pro-S. We choose each of the two atoms in turn giving it higher priority (1H becomes 2H for example) than the other and carry out the usual C-I-P ranking procedure:
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Enantiotopic/ Diastereotopic Faces
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Examples
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You should be able to:
(i) Use R/S configuration according to C-I-P nomenclature.
(ii) Define and use the terms enantiomer and diastereomer.
(iii) Recognise non-carbon atom stereogenic centres.
(iv) Define axial and helical chirality and give examples.
(v) Identify and use prochiral centres and faces.
Outputs